Department of Neuropathology and APHM Tumor Bank, LaTimone Hospital, Marseille, France.
Acta Neuropathol Commun. 2013 May 9;1:10. doi: 10.1186/2051-5960-1-10.
Solitary Fibrous Tumours (SFT) and haemangiopericytomas (HPC) are rare meningeal tumours that have to be distinguished from meningiomas and more rarely from synovial sarcomas. We recently found that ALDH1A1 was overexpressed in SFT and HPC as compared to soft tissue sarcomas. Using whole-genome DNA microarrays, we defined the gene expression profiles of 16 SFT/HPC (9 HPC and 7 SFT). Expression profiles were compared to publicly available expression profiles of additional SFT or HPC, meningiomas and synovial sarcomas. We also performed an immunohistochemical (IHC) study with anti-ALDH1 and anti-CD34 antibodies on Tissue Micro-Arrays including 38 SFT (25 meningeal and 13 extrameningeal), 55 meningeal haemangiopericytomas (24 grade II, 31 grade III), 163 meningiomas (86 grade I, 62 grade II, 15 grade III) and 98 genetically confirmed synovial sarcomas.
ALDH1A1 gene was overexpressed in SFT/HPC, as compared to meningiomas and synovial sarcomas. These findings were confirmed at the protein level. 84% of the SFT and 85.4% of the HPC were positive with anti-ALDH1 antibody, while only 7.1% of synovial sarcomas and 1.2% of meningiomas showed consistent expression. Positivity was usually more diffuse in SFT/HPC compared to other tumours with more than 50% of tumour cells immunostained in 32% of SFT and 50.8% of HPC. ALDH1 was a sensitive and specific marker for the diagnosis of SFT (SE = 84%, SP = 98.8%) and HPC (SE = 84.5%, SP = 98.7%) of the meninges. In association with CD34, ALDH1 expression had a specificity and positive predictive value of 100%.
We show that ALDH1, a stem cell marker, is an accurate diagnostic marker for SFT and HPC, which improves the diagnostic value of CD34. ALDH1 could also be a new therapeutic target for these tumours which are not sensitive to conventional chemotherapy.
孤立性纤维瘤（SFT）和血管外皮细胞瘤（HPC）是罕见的脑膜肿瘤，需要与脑膜瘤区分，更罕见的是与滑膜肉瘤区分。我们最近发现 ALDH1A1 在 SFT 和 HPC 中的表达高于软组织肉瘤。使用全基因组 DNA 微阵列，我们定义了 16 例 SFT/HPC（9 例 HPC 和 7 例 SFT）的基因表达谱。表达谱与其他 SFT 或 HPC、脑膜瘤和滑膜肉瘤的公开表达谱进行比较。我们还使用抗 ALDH1 和抗 CD34 抗体对包括 38 例 SFT（25 例脑膜和 13 例脑膜外）、55 例脑膜血管外皮细胞瘤（24 级 II 期，31 级 III 期）、163 例脑膜瘤（86 级 I 期，62 级 II 期，15 级 III 期）和 98 例经基因确认的滑膜肉瘤的组织微阵列进行了免疫组织化学（IHC）研究。
与脑膜瘤和滑膜肉瘤相比，ALDH1A1 基因在 SFT/HPC 中过度表达。这些发现得到了蛋白质水平的证实。84%的 SFT 和 85.4%的 HPC 与抗 ALDH1 抗体呈阳性，而只有 7.1%的滑膜肉瘤和 1.2%的脑膜瘤表现出一致的表达。与其他肿瘤相比，SFT/HPC 的阳性通常更为弥漫，32%的 SFT 和 50.8%的 HPC 中超过 50%的肿瘤细胞免疫染色。ALDH1 是 SFT（SE=84%，SP=98.8%）和脑膜 HPC（SE=84.5%，SP=98.7%）诊断的敏感和特异性标志物。与 CD34 联合使用时，ALDH1 表达的特异性和阳性预测值为 100%。
我们表明，干细胞标志物 ALDH1 是 SFT 和 HPC 的准确诊断标志物，提高了 CD34 的诊断价值。ALDH1 也可能成为这些对常规化疗不敏感的肿瘤的新治疗靶点。
